MRKAd5 HIV-1 Gag/Pol/Nef Vaccine-Induced T-Cell Responses Inadequately Predict Distance of Breakthrough HIV-1 Sequences to the Vaccine or Viral Load

Background: The sieve analysis for the Step trial found evidence that breakthrough HIV-1 sequences for MRKAd5/HIV-1 Gag/Pol/Nef vaccine recipients were more divergent from the vaccine insert than placebo sequences in regions with predicted epitopes. We linked the viral sequence data with immune response and acute viral load data to explore mechanisms for and consequences of the observed sieve effect. Methods: Ninety-one male participants (37 placebo and 54 vaccine recipients) were included; viral sequences were obtained at the time of HIV-1 diagnosis. T-cell responses were measured 4 weeks post-second vaccination and at the first or second week post-diagnosis. Acute viral load was obtained at RNA-positive and antibody-negative visits. Findings: Vaccine recipients had a greater magnitude of post-infection CD8+ T cell response than placebo recipients (median 1.68% vs 1.18%; p = 0.04) and greater breadth of post-infection response (median 4.5 vs 2; p = 0.06). Viral sequences for vaccine recipients were marginally more divergent from the insert than placebo sequences in regions of Nef targeted by pre-infection immune responses (p = 0.04; Pol p = 0.13; Gag p = 0.89). Magnitude and breadth of pre-infection responses did not correlate with distance of the viral sequence to the insert (p. 0.50). Acute log viral load trended lower in vaccine versus placebo recipients (estimated mean 4.7 vs 5.1) but the difference was not significant (p = 0.27). Neither was acute viral load associated with distance of the viral sequence to the insert (p>0.30). Interpretation: Despite evidence of anamnestic responses, the sieve effect was not well explained by available measures of T-cell immunogenicity. Sequence divergence from the vaccine was not significantly associated with acute viral load. While point estimates suggested weak vaccine suppression of viral load, the result was not significant and more viral load data would be needed to detect suppression.

International collaborative project to compare and monitor the nutritional composition of processed foods

Background: Chronic diseases are the leading cause of premature death and disability in the world with overnutrition a primary cause of diet-related ill health. Excess energy intake, saturated fat, sugar, and salt derived from processed foods are a major cause of disease burden. Our objective is to compare the nutritional composition of processed foods between countries, between food companies, and over time. Design: Surveys of processed foods will be done in each participating country using a standardized methodology. Information on the nutrient composition for each product will be sought either through direct chemical analysis, from the product label, or from the manufacturer. Foods will be categorized into 14 groups and 45 categories for the primary analyses which will compare mean levels of nutrients at baseline and over time. Initial commitments to collaboration have been obtained from 21 countries. Conclusions: This collaborative approach to the collation and sharing of data will enable objective and transparent tracking of processed food composition around the world. The information collected will support government and food industry efforts to improve the nutrient composition of processed foods around the world.

Multiple Intravenous Administrations of Human Umbilical Cord Blood Cells Benefit in a Mouse Model of ALS

Background: A promising therapeutic strategy for amyotrophic lateral sclerosis (ALS) is the use of cell-based therapies that can protect motor neurons and thereby retard disease progression. We recently showed that a single large dose (25x10(6) cells) of mononuclear cells from human umbilical cord blood (MNC hUCB) administered intravenously to pre-symptomatic G93A SOD1 mice is optimal in delaying disease progression and increasing lifespan. However, this single high cell dose is impractical for clinical use. The aim of the present pre-clinical translation study was therefore to evaluate the effects of multiple low dose systemic injections of MNC hUCB cell into G93A SOD1 mice at different disease stages. Methodology/Principal Findings: Mice received weekly intravenous injections of MNC hUCB or media. Symptomatic mice received 10(6) or 2.5x10(6) cells from 13 weeks of age. A third, pre-symptomatic, group received 10(6) cells from 9 weeks of age. Control groups were media-injected G93A and mice carrying the normal hSOD1 gene. Motor function tests and various assays determined cell effects. Administered cell distribution, motor neuron counts, and glial cell densities were analyzed in mouse spinal cords. Results showed that mice receiving 10(6) cells pre-symptomatically or 2.5x10(6) cells symptomatically significantly delayed functional deterioration, increased lifespan and had higher motor neuron counts than media mice. Astrocytes and microglia were significantly reduced in all cell-treated groups. Conclusions/Significance: These results demonstrate that multiple injections of MNC hUCB cells, even beginning at the symptomatic disease stage, could benefit disease outcomes by protecting motor neurons from inflammatory effectors. This multiple cell infusion approach may promote future clinical studies.

Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC

We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.

IINTERNATIONAL STRATEGY FOR AN EMERGING MULTINATIONAL IN BRAZIL: THE CASE OF JBS

The focus of this study is on questioning whether the traditional theories of internationalization are adequate to explain the international expansion of multinationals from emerging countries. Looking forward on this issue, we investigate the internationalization strategies adopted by JBS, a Brazilian multinational of the beef industry. The results show that the company adopted two of the five generic strategies specific to the context of emerging countries suggested by Ramamurti and Singh (2009): global consolidator and vertical integrator. Moreover, when analyzing the internationalization of the company under study, the speed of the process is highlighted when compared to traditional multinationals. It is concluded that the main mode of entry that allowed the international expansion was the acquisition and that this strategy has advantages to the company, such as access to strategic resources and rapid growth, possibly overcoming the liability of foreignness, the opportunity to compete globally and the diversification of segments that generate synergies to the company's activities.

Linear viscoelasticity of immiscible blends: The application of creep

A new method to characterize the long-time linear relaxation mechanisms of immiscible blends based on creep experiment was developed. Small-amplitude oscillatory shear and incomplete creep/recovery experiments were combined to characterize immiscible blends of polypropylene with dispersed droplets of polystyrene. An experimental protocol was defined such that the full creep compliance function could be obtained while minimizing morphological changes. Dynamic experiments were performed to characterize the shorter time relaxation processes, and creep and recovery measurements were used to detect the longer time portions of the relaxation spectra. Extended retardation and relaxation spectra were constructed by combining these data. It was found that using this technique, very long-time relaxation peaks which were inaccessible with dynamic experiments alone could be detected. (C) 2012 The Society of Rheology. [http://dx.doi.org/10.1122/1.4720081]

The Southern Ocean and Its Climate in CCSM4

The new Community Climate System Model, version 4 (CCSM4), provides a powerful tool to understand and predict the earth's climate system. Several aspects of the Southern Ocean in the CCSM4 are explored, including the surface climatology and interannual variability, simulation of key climate water masses (Antarctic Bottom Water, Subantarctic Mode Water, and Antarctic Intermediate Water), the transport and structure of the Antarctic Circumpolar Current, and interbasin exchange via the Agulhas and Tasman leakages and at the Brazil-Malvinas Confluence. It is found that the CCSM4 has varying degrees of accuracy in the simulation of the climate of the Southern Ocean when compared with observations. This study has identified aspects of the model that warrant further analysis that will result in a more comprehensive understanding of ocean-atmosphere-ice dynamics and interactions that control the earth's climate and its variability.